Description: This proposal is based upon the hypothesis that evaluation of changes in gene expression in response to specific stimuli will lead to identification of glaucoma genes that are involved in loss of intraocular pressure homeostasis. By utilizing the known glaucoma gene, TIGR, and evaluating the response of gene expression in relation to changes in TIGR levels, the PI anticipates that additional glaucoma genes will be identified. Four specific aims are outlines. The first will use microarray technology to establish expression profiles of human trabecular meshwork cells (HTM) in response to aqueous, glaucoma medications and other inducing agents. The second aim will analyze genes identified in aim 1 that may be a part of a pathway including TIGR and place the gene upstream or downstream of TIGR. The third aim will determine which of the genes identified in specific aim 1 map to glaucoma locus genetic inclusion intervals. These genes will be screened for mutations in glaucoma and control populations. The final specific aim will carry out genotype/phenotype studies of TIGR and newly identified glaucoma genes. The long term goal of this lab is to elucidate the underlying causes of glaucoma and the accompanying pathogenic processes.